AUTHOR=Peirone Serena , Tirtei Elisa , Campello Anna , Parlato Caterina , Guarrera Simonetta , Mareschi Katia , Marini Elena , Asaftei Sebastian Dorin , Bertero Luca , Papotti Mauro , Priante Francesca , Perrone Sarah , Cereda Matteo , Fagioli Franca 

TITLE=Impaired neutrophil-mediated cell death drives Ewing’s Sarcoma in the background of Down syndrome

JOURNAL=Frontiers in Oncology

VOLUME=Volume 14 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1429833

DOI=10.3389/fonc.2024.1429833

ISSN=2234-943X

ABSTRACT=IntroductionEwing Sarcoma (EWS) has been reported in seven children with Down syndrome (DS). To date, a detailed assessment of this solid tumour in DS patients is yet to be made.MethodsHere, we characterise a chemo-resistant mediastinal EWS in a 2-year-old DS child, the youngest ever reported case, by exploiting sequencing approaches.ResultsThe tumour showed a neuroectodermal development driven by the EWSR1-FLI1 fusion. The inherited myeloperoxidase deficiency of the patient caused failure of neutrophil-mediated cell death and promoted genomic instability.DiscussionIn this context, the tumour underwent genome-wide near haploidisation resulting in a massive overexpression of pro-inflammatory cytokines. Recruitment of defective neutrophils fostered rapid evolution of this EWS.